Asthma is the most common chronic disease of childhood in the United States, causes significant morbidity, particularly in the inner-city, and accounts for billions of dollars in health care utilization, despite aggressive measures to identif remediable causes. Home environments are established sources of exposure that exacerbate symptoms and home-based interventions are proven effective. Prior to the inception of the School Inner-City Asthma Study (SICAS-1), no American study had comprehensively evaluated the relationship between urban exposures in school, classroom, and home environments and asthma morbidity. Nearly all elementary school children spend 7 to 12 hours a day in school, and most of that time is spent in one classroom. From SICAS-1, we learned that student classroom-specific mouse allergen, mold, and particulate pollutant exposure is associated with worsening symptoms. We also demonstrated our ability to reduce these exposures in a busy, school setting. Our proposal builds upon our established, successful school-based infrastructure to determine whether a school/classroom intervention will efficiently and effectively improve asthma morbidity by reducing these exposures. Our goal is to determine the efficacy of school/classroom based environmental intervention in reducing asthma morbidity in urban schoolchildren. Our central hypothesis is that reducing classroom/school exposure to mouse allergen, mold, and particulate pollutants will decrease asthma morbidity in students with asthma. We plan to test this hypothesis in an intervention study of 300 elementary students with asthma from multiple classrooms in 40 Boston inner-city elementary schools. Our clinical trial aims are to determine the effectiveness of a school/classroom based environmental intervention (school integrated pest management and classroom air purifying filter units within these schools) to reduce asthma morbidity. Our mechanistic aim is to test the hypothesis that effects of school/classroom- based environmental interventions on symptoms/other measures of asthma control occur through changes in gene methylation or expression in pathways (and secondarily, in genes) relevant to airway function and asthma. This will expand our understanding of asthma immunopathogenesis and create opportunities to identify potential novel targets for asthma therapy. Within pathways or networks of genes we will (a) determine how our interventions influence changes in nasal airway cell methylation or gene expression; (b) evaluate how our intervention-associated changes in methylation and gene expression influence asthma outcomes; and (c) estimate through mediation analysis how much of the intervention effects on asthma symptoms occurs through methylation/gene expression changes. This study is an unprecedented, high impact opportunity to test whether we can efficiently benefit a community of children in the school environment as opposed to individuals in single homes. It also adds a novel mechanistic application on health outcomes. It efficiently tackles a critical public health problem that affects a growing proportion of disadvantaged, urban U.S. children.